Ch 7 - Substitution Reactions Flashcards
(65 cards)
1
Q
substitution Reaction
A
a reaction where one group is exchanged for another
- X group is replaced with Y but the rest of the structure remains the same
2
Q
elimination reaction
A
a reaction one group is removed via the formation of a pie bond
3
Q
substitution and elimination reactions are often in
A
competition with each other
4
Q
a substitution reaction can occur when
A
a suitable electrophile is treated with a nucleophile
5
Q
substrate
A
term used to describe the electrophile in a substitution reaction
- leaving group – A group capable of separating from the substrate - must be present for a substrate to function
6
Q
a leaving group serves 2 functions with the substrate
A
- withdraws electron density via induction creating an electrophilic carbon
- stabilizes any negative charge which may develop as a result of the leaving group separating from the substrate
- Halogens are very common leaving groups(fill octet easily)
7
Q
when a chirality center is present the configuration must be indicated
A
at the start of the same in (R/S)
8
Q
haloalkane
A
the systemic IUPAC name treats a halogen as a substituent
9
Q
alkyl halide(organohalide)
A
the common name treats the compound as an alkyl substituent connected to a halide
10
Q
alpha(fish sign) position
A
the carbon connected directly to the halogen
11
Q
Beta(B) positions
A
carbon atoms connected to the alpha position
12
Q
each carbon is described in terms of its proximity to
A
the halogen
13
Q
an alkyl halide will have
A
1 alpha position and up to 3 beta positions
14
Q
alkyl halides are classified as
A
primary(1 naught), secondary(2 naught), or tertiary(3 naught) based on the number of alkyl groups connected to the alpha position
15
Q
organohalides arevery stable and often toxic
A
persist and accumulate in the environment
16
Q
PCBs(polychlorinated biphenyls) accumulated in the environment and threated significant portions of wildlife and were banned
A
organhalide
17
Q
organohalides serve a variety of functions in living organisms
A
- defense mechanisms(poison = chemical warfare)
- hormones(chemical messages to specific target cells)
18
Q
not all halogenated compounds are toxic
A
sucralose(Splenda - artificial sweetener) is a halogenated compound we eat
19
Q
every substitution reaction involved at least 2 of the 4 arrow pushing patterns
A
nucleophilic attack and loss of a leaving group
20
Q
in a concerted process
A
nucleophilic attack and loss of the leaving group occur simultaneously
21
Q
in a stepwise process
A
loss of the leaving group occurs first followed by nucleophilic attack
22
Q
remember:
NaOH is a hydroxide ion(HO-)
A
the Na+ is just a counter ion and can largely be ignored
23
Q
always draw all groups of a tertiary carbocation as
A
far apart as possible
24
Q
Sn2 mechanism
rate = k[substrate][nucleophile]
A
- 2nd order reaction
- doubling the concentration of the substrate or nucleophile will cause the reaction rate to double
- there must be a step in which the nucleophile and substrate collide
25
bimolecular
a step which two chemical entities collide
26
Sn2
- S = substitution
- n = nucleophilic
- 2 = bimolecular
- consistent with a concerted mechanism
27
Sn2 mechanism
when the alpha position is a chirality center a change in configuration is generally observed
and S reactant will become an R product
28
Sn2 mechanism
inversion of configuration
when a reactant is S configuration and results in an R configuration product(or the other way around)
- “Walden” inversion
29
Sn2 mechanism
back-side attack
the requirement for inversion of configuration means the nucleophile can only attack from the back side(the side opposite the leaving group)
30
Sn2 mechanism
2 explanations for inversion of configuration through a back side attack
- the lone pairs of the leaving group create regions of high electron density that effectively block the front side of the substrate
- nucleophile can only approach from the back side
- according to MO theory, an attack from the back will allow the nucleophiles HOMO and the LUMO of the electrophile to overlap creating an efficient bond
- from the front there is a node which will not bond
31
the Sn2 process(inversion of configuration) is consistent with
a concerted mechanism because as the loss of leaving group occurs and the nucleophile attacks the backside the chirality must flip like an umbrella in the wind
32
stereospecific
the configuration of the product is dependent on the configuration of the starting material
33
the higher the Ea for the starting alkyl halide the slower the reaction
- Me > primary > secondary > tertiary
- Me is the most reactive
- H will hold electrons less strongly than tertiary with 3 R groups
- H will have lower Ea as its an easier bond to break
- less sterically hindered
34
stepwise reaction
- loss of leaving group to form a carbocation intermediate
| - nucleophilic attack on the carbocation intermediate
35
rate determining step(RDS)
the step with the highest energy transition determines the rate for the overall process
36
unimolecular
the step involved only one chemical entity
- first order reaction
- rate = k[substrate]
37
Sn1
- s = substitution
- n = nucleophilic
- 1 = unimolecular
38
unimolecular means there is only one chemical entity participating in the rate determining step of the reaction
the rate of the reaction is not dependent on how much nucleophile is present
39
an excess of nucleophile will not
speed the reaction up but it must be present
for Sn1
40
the rate of a Sn1 reaction is highly dependent on the nature of the substrate
- least stable -> most stable(methane
41
tertiary substrates generally undergo substitution via Sn1 process
primary substrates go Sn2
42
secondary substrates can proceed via
either Sn1 or Sn2 depending
43
retention of configuration
Sn1 reactions form intermediate carbocations which can then be attacked from either side
- can either keep its configuration or have an inversion of configuration
- theoretically should produce a racemic mixture but typically slightly more form inversion product
- slightly blocked front from the ion pair favors a backside attack by an unhindered nucleophile
44
every Sn1 reaction has at least two steps
- loss of a leaving group
| - nucleophilic attack
45
3 other possibilities in a Sn1 mechanism(loss of a leaving group followed by a nucleophilic attack)
- before the two core steps – proton transfer
- between the two core steps – a carbocation rearrangement
- after the two core steps – proton transfer
46
proton transfer before the two core steps(Sn1 reaction)
- necessary whenever the substrate is an alcohol(ROH)
- OH- is a bad leaving group but H2O is an excellent leaving group
- if the substrate has no leaving group other than OH- then acidic conditions will be required in order to allow an Sn1 reaction
47
Proton transfer after the two core steps(Sn1 reaction)
- necessary whenever the nucleophile is neutral(not negatively charged)
- the species ends positively charged and must have a proton to balance it
- solvolysis – the solvent functions as the nucleophile in a reaction
48
Carbocation Rearrangements during an Sn1 process
- when carbocation is possible a mixture of products is generally obtained
- products with and without the rearrangement
- the ratio depends on if the rearrangement takes place more quickly than the nucleophilic attack
- in most cases the rearranged products predominates the nucleophilic attack process
- intramolecular process typically occur more rapidly then intermolecular processes
49
there can be before and/or after Sn2(concerted process = no carbocation rearrangement possible)
- proton transfer before
| - proton transfer after
50
a proton transfer is required before a Sn2 reaction if
an alcohol(to make a good leaving group)
51
a proton transfer is required after a Sn2 reaction if
the nucleophile is neutral(charge balance the +)
52
a primary substrate will be
an Sn2 process
53
Sn1 factors to look for
racemization(no inversion with chirality) and rearrangement
54
Sn2 factors to look for
inversion of configuration(chirality) and rearrangement is not possible
55
4 major factors to determine if Sn1 or Sn2
- the substrate
- the leaving group
- the nucleophile
- the solvent
56
identifying the substrate is the most important factor in determining if
Sn1 or Sn2
57
4 major factors to determine if Sn1 or Sn2
The substrate
- most important factor to determine Sn2 or Sn1
- Sn1 is determined by carbocation stability(Tertiary best and Me worst)
- Sn2 is determined by steric hindrance in the transition state(Me best and tertiary worst)
- Methy and primary substrates favor Sn2
- Tertiary substrates favor Sn1
- Secondary substrates must be determined by the other three factors(leaving group, nucleophile, and solvent)
- allylic halides and benzylic halides can react via Sn2 or Sn1 processes
- Vinyl halides and Aryl halides are unreactive and do not respond to either Sn1 or Sn2
- would generate an unstable carbocation
- Sn2 reactions are generally not observed at sp2 hybridized centers(back side attack is sterically encumbered)
58
4 major factors to determine if Sn1 or Sn2
The Nucleophile
- Sn2 is affected by the concentration and strength of the nucleophile
- a strong nucleophile will speed up the rate of an Sn2 reaction
- a weak nucleophile will slow down the rate of an Sn2 reaction
- Sn1 process is not affected by the concentration or strength of the nucleophile because the nucleophile does not participate in the rate determining step
- A strong nucleophile favors Sn2
- a weak nucleophile disfavors Sn2(thereby allowing Sn1 to compete successfully)
- Strong nucleophiles:
- I-, HS-, HO-, Br-, H2S, RO-, Cl-,RSH, N-=C-
- Weak nucleophiles:
- F-, H2O, ROH
- F- is weak in protic solvents but strong in polar aprotic solvents
59
4 major factors to determine if Sn1 or Sn2
The leaving group
- both Sn1 and Sn2 are sensitive to the leaving group
- Sn1 generally more sensitive
- a bad leaving group will disallow either Sn1 or Sn2 reactions
- the leaving group must be highly stabilized in order for an Sn1 reaction to be effective
- in general, good leaving groups are the conjugate bases of strong acids
- Iodide is one of the best leaving groups
- Good leaving groups
- I-, Br-, Cl-, SO3-. H2O
- bad leaving groups
- HO-, CH3CH2O-, (CH3)3CHO-,NH2-
- sulfonate ions – the most commonly used leaving groups aside from halides
- Halides
- I-, Br-, Cl-
- sulfonate ions
- SO3-
60
4 major factors to determine if Sn1 or Sn2
Solvent Effects
- protic solvents – contain at least one hydrogen atom connected directly to an electronegative atom
- polar aprotic solvents – contain no hydrogen atoms connected directly to an electronegative atom
- protic solvents are used for Sn1 reactions
- polar aprotic solvents are used to favor Sn2 reactions
- in protic solvents:
- I- >Br- >Cl- >F-
- I- is the strongest nucleophile and fluoride is the weakest
- In polar aprotic solvents:
- F- > Cl- > Br- > I-
- F- is the strongest nucleophile
- Fluoride becomes the strongest because it is the least stable anion
61
4 factors summary:
- Substrate
- Methyl or primary (Sn2)
- tertiary (Sn1)
- Nucleophile
- Strong nucleophile(Sn2)
- weak nucleophile(Sn1)
- Leaving Group
- Good leaving group(Sn2)
- Excellent leaving group(Sn1)
- Solvent
- polar aprotic(Sn2)
- Protic(Sn1)
62
3 major considerations for selecting the reagent to accomplish functional group transformation
- the substrate
- nucleophile and solvent
- leaving group
63
the substrate
- methyl or primary dictates an Sn2 process
- tertiary dictates an Sn1 process
- secondary is generally Sn2 as it avoids carbocation rearrangement
64
Nucleophile and the Solvent
- Sn1 requires a weak nucleophile and protic solvent
| - Sn2 requires a strong nucleophile and polar aprotic solvent
65
leaving group
- OH is a bad leaving group and must be converted to a good leaving group
- Sn1 process an acid is used to protonate the OH group(converting to an excellent leaving group)
- Sn2 reactions OH is converted into tosylate(SO3-) an excellent leaving group rather than protenating the group
